A hepatitis C virus envelope polymorphism confers resistance to neutralization by polyclonal sera and broadly neutralizing monoclonal antibodies

Lisa N. Wasilewski, Ramy El-Diwany, Supriya Munshaw, Anna E. Snider, Jillian K. Brady, William O. Osburn, Stuart C. Ray, Justin R. Bailey

Research output: Contribution to journalArticle

Abstract

Hepatitis C virus (HCV) infection is a global health problem, with millions of chronically infected individuals at risk for cirrhosis and hepatocellular carcinoma. HCV vaccine development is vital in the effort toward disease control and eradication, an undertaking aided by an increased understanding of the mechanisms of resistance to broadly neutralizing antibodies (bNAbs). In this study, we identified HCV codons that vary deep in a phylogenetic tree of HCV sequences and showed that a polymorphism at one of these positions renders Bole1a, a computationally derived, ancestral genotype 1a HCV strain, resistant to neutralization by both polyclonal-HCV-infected plasma and multiple broadly neutralizing monoclonal antibodies with unique binding epitopes. This bNAb resistance mutation reduces replicative fitness, which may explain the persistence of both neutralizationsensitive and neutralization-resistant variants in circulating viral strains. This work identifies an important determinant of bNAb resistance in an ancestral, representative HCV genome, which may inform HCV vaccine development.

Original languageEnglish (US)
Pages (from-to)3773-3782
Number of pages10
JournalJournal of virology
Volume90
Issue number7
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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